Rat mast cell heparin proteoglycan which has an estimated molecular weight of 750,000 is cleaved to molecules of less than 10,000 upon exposure to H2O2 and ferrous ion (Fenton's reagent). This cleavage is inhibited by catalase and by the hydroxyl radical scavenger mannitol. Heparin, as a component of intact mast cell granules, also is cleaved with H2O2 and Fe2+. These studies suggest that activated phagocytes which generate oxygen radicals contribute to the degradation of both solubilized and granule-associated proteoglycan heparin. Rat bone marrow-derived mucosal mast cells synthesize a chondroitin sulfate proteoglycan. Disaccharide analysis shows the predominant sulfated disaccharide to be chondroitin 4-sulfate. Mast cells were seen in 27 out of 35 synovial fluids. There was a strong correlation between mast cell number and histamine content. No relationship between mast cell number and diagnosis was observed except in patients with mastocytosis. Synovial fluid mast cells released histamine upon exposure to anti-human IgE, and contained a tryptase previously identified in human lung mast cells. In syniovial biopsies from 20 patients with rheumatoid arthritis, mast cell infiltrations were shown to correlate with T helper/inducer lymphocytes. Mast cell numbers were dramatically decreased by intra-articular steroid injection, but not by methotrexate therapy. Endothelial cells in culture produce a factor which causes proliferation of the IL-3 dependent mast cell line PT-18.